Identification, Characterization, and Heritability of Murine Metastable Epialleles: Implications for Non-genetic Inheritance

• Anastasiya Kazachenka ^[1] ; Tessa M. Bertozzi ^[1] ; Marcela K. Sjoberg Herrera ^[2]
  1. [1] University of Cambridge

     University of Cambridge

     Cambridge District, Reino Unido

     
  2. [2] Wellcome Trust Sanger Institute

     Wellcome Trust Sanger Institute

     Cambridge District, Reino Unido

     
• Localización: Cell, ISSN 0092-8674, Vol. 175, Nº. 5, 2018, págs. 1259-1271
• Idioma: inglés
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• Resumen

  • Generally repressed by epigenetic mechanisms, retrotransposons represent around 40% of the murine genome. At the Agouti viable yellow (Avy) locus, an endogenous retrovirus (ERV) of the intracisternal A particle (IAP) class retrotransposed upstream of the agouti coat-color locus, providing an alternative promoter that is variably DNA methylated in genetically identical individuals. This results in variable expressivity of coat color that is inherited transgenerationally. Here, a systematic genome-wide screen identifies multiple C57BL/6J murine IAPs with Avy epigenetic properties. Each exhibits a stable methylation state within an individual but varies between individuals. Only in rare instances do they act as promoters controlling adjacent gene expression. Their methylation state is locus-specific within an individual, and their flanking regions are enriched for CTCF. Variably methylated IAPs are reprogrammed after fertilization and re-established as variable loci in the next generation, indicating reconstruction of metastable epigenetic states and challenging the generalizability of non-genetic inheritance at these regions.